A Study to Collect Bone Marrow for Process Development and Production of BM-MSC to Treat Severe COVID19 Pneumonitis (COMET20d)

A Study to Collect Bone Marrow for Process Development and Production of Bone Marrow Mesenchymal Stromal Cells to Treat Severe COVID19 Pneumonitis

The COVID-19 pandemic, commonly referred to as "coronavirus", first began in the city of Wuhan, China in December 2019. This virus has since spread globally, with infections reported in nearly every country. COVID-19 targets the body's respiratory system, where infections can be found in the nose, throat and lungs. The effect of COVID-19 infection is very variable, where many people might not know that they have been infected and have recovered from COVID-19. However, COVID-19 infection can cause people to have difficulty breathing. This can be severe enough to require hospitalisation and potentially intensive care treatment.

While they are being treated in hospital, COVID-19 infected patients can be found to have inflamed tissue in their lungs (referred to medically as "pneumonitis"). This inflammation is thought to be caused by their body's immune systems overacting to the infection rather than the COVID-19 virus itself. By potentially dampening down this overreaction of their immune system, it is hoped that COVID-19 patients with inflamed lungs have better and quicker chance to survive.

Mesenchymal stromal cells (MSCs) have been shown to have anti-inflammatory and healing properties on injured tissue. MSCs have been trialled in various diseases but have not yet been tested on patients with COVID-19. In this study, the investigators will obtain bone marrow from healthy volunteers to develop a cell-based treatment for COVID-19-related pneumonitis. The investigators will also determine whether it is feasible to recruit bone marrow donors in a clinically useful timeframe to treat COVID-19 patients. A future trial, COMET20, will use the bone marrow-derived MSCs (BM-MSCs) manufactured in COMET20d to treat COVID-19 patients suffering with pneumonitis, to determine whether the BMMSCs can reduce the likelihood for mechanical ventilation and reduce hospitalisation.

Study Overview

• Status: Unknown
• Conditions: Healthy Volunteers for Bone Marrow Donation
• Intervention / Treatment: Procedure: Bone Marrow Harvest

• Study Type: Observational
• Enrollment (Anticipated): 10

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Cambridge University Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy adults aged 18-40 years who are negative for mandatory infectious disease markers including current COVID-19 infection.

Description

Inclusion Criteria:

• Have given written informed consent to participate
• Be aged between 18 and 40 years old
• Have Eastern Cooperative Oncology Group (ECOG) performance status 0
• Be negative for mandatory infectious disease markers (IDM) as per World Marrow Donor Association (WMDA) guidelines
• Present a negative SARS-CoV2 screen
• Show absence of clinical symptoms of COVID-19 (Not have been in known COVID-19 contact within the previous 14 days, Adherence to national social distancing guidelines for 14 days)
• Have a BMI <35kg/m^2
• Women of childbearing potential need a negative pregnancy test (urine or blood) within 7 days prior to the marrow collection

Exclusion Criteria:

• Any major disease which would represent a contraindication to bone marrow donation based on WMDA guidelines
• Presence of any previous or active malignancy (other than non-melanoma skin cancer)
• Any other concurrent severe and/or uncontrolled medical condition
• Women who are pregnant or breast-feeding
• Any acute or chronic back complaint
• Presence of anaesthetic risk factors

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Volunteer; A one time only 30-80 mL sample of bone marrow will be collected from both posterior superior iliac crests.	Procedure: Bone Marrow Harvest; Healthy volunteer bone marrow harvest

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine feasibility of recruiting healthy volunteers in a clinically useful timeframe.	Successful identification of healthy volunteers in acceptable timeframe (i.e. within days) to donate bone marrow.	3 or more participants recruited in 1 month
Manufacture a cell-based product suitable for clinical use	Successful manufacture of bone marrow-mesenchymal stromal cells suitable for clinical use	Successfully opening the next phase of the trial in approx. 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establishment of a robust process of production	Ability to prepare a dossier acceptable to the MHRA. Success will achieved if the dossier is deemed acceptable.	Successfully opening the next phase of the trial in approx. 2 months
Production of stability data to be used in the MHRA dossier for the COMET clinical trial.	Successful manufacturing of products will be defined initially as the award of a Manufacturers Specials Licence to the CCTL to allow the manufacture of Bone Marrow-Mesenchymal Stromal Cells for compassionate use.	Successfully opening the next phase of the trial in approx. 2 months
Production of cell-based products to be administered to COVID-19 patients with severe pneumonitis.	Successful manufacturing of products will be subsequently defined by production under MA(IMP) licence, allowing for future production under CTIMP and CTA.	Successfully opening the next phase of the trial in approx. 2 months
Analysis of cells for understanding production, manufacture and related research.	Successful manufacturing of products, under MA(IMP) licence will be defined as the availability of Bone Marrow-Mesenchymal Stromal Cells to be used in the context of the COMET20 clinical trial.	Successfully opening the next phase of the trial in approx. 2 months

Collaborators and Investigators

• Sponsor: CCTU- Cancer Theme
• Collaborators: Cambridge Cellular Therapies Laboratory; The Evelyn Trust
• Investigators: Principal Investigator: Andrew McCaskie, FRCS, University of Cambridge & Cambridge University Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2020
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: May 13, 2020
• First Submitted That Met QC Criteria: May 20, 2020
• First Posted (Actual): May 21, 2020

Study Record Updates

• Last Update Posted (Actual): May 21, 2020
• Last Update Submitted That Met QC Criteria: May 20, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia
• Other Study ID Numbers: COMET20d

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No